Medical Oncology

, 30:666 | Cite as

The basic helix-loop-helix (bHLH) proteins in breast cancer progression

  • Nuzhat N. Kabir
  • Lars Rönnstrand
  • Julhash U. Kazi
Letter to the Editor

The basic helix-loop-helix (bHLH) proteins are the major transcription factors acting as transcriptional enhancers or inhibitors of various genes through binding to the canonical E-box sequence. The bHLH proteins are highly conserved in both vertebrates and invertebrates. The bHLH domain is approximately 60 amino acids in length consisting of a DNA-binding basic region followed by two alpha-helices separated by a variable loop. The DNA-binding basic region associates with the hexanucleotide E-box sequence. The human genome contains 121 bHLH genes which regulate various cellular processes including embryonic development [1, 2]. Many of them are involved in cell proliferation, differentiation and oncogenesis, as well as apoptosis. For example, MyoD and NeuroD family bHLH proteins contribute to myogenesis, neurogenic differentiation and pancreatic development, while Myc family bHLH proteins are directly involved in cell differentiation, proliferation and oncogenesis [3].

The bHLH proteins...


Breast Cancer Principal Component Analysis Analysis bHLH Protein bHLH Gene NCBI Gene Expression Omnibus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Conflict of interest

The authors declare no conflict of interest.

Supplementary material

12032_2013_666_MOESM1_ESM.pdf (6.4 mb)
Supplementary material 1 (PDF 6571 kb)


  1. 1.
    Kabir NN, Hossain MI, Kazi JU. Comparative studies on human and rat basic helix-loop-helix proteins. Asian J Biol Sci. 2011;4(8):601–8. doi: 10.3923/ajbs.2011.601.608.CrossRefGoogle Scholar
  2. 2.
    Jones S. An overview of the basic helix-loop-helix proteins. Genome Biol. 2004;5(6):226. doi: 10.1186/gb-2004-5-6-226.PubMedCrossRefGoogle Scholar
  3. 3.
    Desprez PY, Sumida T, Coppe JP. Helix-loop-helix proteins in mammary gland development and breast cancer. J Mammary Gland Biol Neoplasia. 2003;8(2):225–39.PubMedCrossRefGoogle Scholar
  4. 4.
    Kazi JU, Ronnstrand L. Suppressor of cytokine signaling 2 (SOCS2) associates with FLT3 and negatively regulates downstream signaling. Mol oncol. 2013;7(3):693–703. doi: 10.1016/j.molonc.2013.02.020.PubMedCrossRefGoogle Scholar
  5. 5.
    Kabir NN, Ronnstrand L, Kazi JU. Protein kinase C expression is deregulated in chronic lymphocytic leukemia. Leuk Lymphoma. 2013;. doi: 10.3109/10428194.2013.769220.PubMedGoogle Scholar
  6. 6.
    Kabir NN, Ronnstrand L, Kazi JU. Deregulation of protein phosphatase expression in acute myeloid leukemia. Med Oncol. 2013;30(2):517. doi: 10.1007/s12032-013-0517-8.PubMedCrossRefGoogle Scholar
  7. 7.
    Kazi JU, Sun J, Phung B, Zadjali F, Flores-Morales A, Ronnstrand L. Suppressor of cytokine signaling 6 (SOCS6) negatively regulates FLT3 signal transduction through direct binding to phosphorylated tyrosines 591 and 919 of FLT3. J Biol Chem. 2012;287(43):36509–17. doi: 10.1074/jbc.M112.376111.PubMedCrossRefGoogle Scholar
  8. 8.
    Kazi JU, Ronnstrand L. FLT3 signals via the adapter protein Grb10 and overexpression of Grb10 leads to aberrant cell proliferation in acute myeloid leukemia. Mol Oncol. 2013;7(3):402–18. doi: 10.1016/j.molonc.2012.11.003.PubMedCrossRefGoogle Scholar
  9. 9.
    Kazi JU, Ronnstrand L. Src-Like adaptor protein (SLAP) binds to the receptor tyrosine kinase Flt3 and modulates receptor stability and downstream signaling. PloS One. 2012;7(12):e53509. doi: 10.1371/journal.pone.0053509.PubMedCrossRefGoogle Scholar
  10. 10.
    Wu Y, Sato F, Bhawal UK, Kawamoto T, Fujimoto K, Noshiro M, Morohashi S, Kato Y, Kijima H. Basic helix-loop-helix transcription factors DEC1 and DEC2 regulate the paclitaxel-induced apoptotic pathway of MCF-7 human breast cancer cells. Int J Mol Med. 2011;27(4):491–5. doi: 10.3892/ijmm.2011.617.PubMedGoogle Scholar
  11. 11.
    Liu Y, Sato F, Kawamoto T, Fujimoto K, Morohashi S, Akasaka H, Kondo J, Wu Y, Noshiro M, Kato Y, Kijima H. Anti-apoptotic effect of the basic helix-loop-helix (bHLH) transcription factor DEC2 in human breast cancer cells. Genes Cells. 2010;15(4):315–25. doi: 10.1111/j.1365-2443.2010.01381.x.PubMedCrossRefGoogle Scholar
  12. 12.
    Swarbrick A, Akerfeldt MC, Lee CS, Sergio CM, Caldon CE, Hunter LJ, Sutherland RL, Musgrove EA. Regulation of cyclin expression and cell cycle progression in breast epithelial cells by the helix-loop-helix protein Id1. Oncogene. 2005;24(3):381–9. doi: 10.1038/sj.onc.1208188.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Nuzhat N. Kabir
    • 1
  • Lars Rönnstrand
    • 2
  • Julhash U. Kazi
    • 1
    • 2
  1. 1.Laboratory of Computational BiochemistryKN Biomedical Research InstituteBarisalBangladesh
  2. 2.Experimental Clinical Chemistry, Department of Laboratory Medicine, Wallenberg LaboratoryLund University, Skåne University HospitalMalmöSweden

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